Vaccine and Infectious Disease Division

Evaluating the impact of efficacy dilution in microbicide trials

Various topical microbicide gels for vaginal use have been studied as candidates to prevent HIV infection in women but were found either ineffective or harmful. But certain conditions in the trials such as improper use of the gel might mask the gels’ true efficacy.  To evaluate how much different conditions might be masking the efficacy of the gels to prevent HIV infection (also termed “efficacy dilution”), VIDI associate member Dr. BenoÎt Mâsse and colleagues investigated the efficacy dilution under four different conditions: adherence to use of the product every time the trial participants had sex, time without product use due to pregnancy, HIV infection due to unprotected anal intercourse, and the efficacy of the placebo gel in preventing HIV infection.  In a typical microbicide trial, some or all of these dilution factors will be present, and could contribute substantially to overall dilution effect if multiple factors are present.

The researchers found that each of these four scenarios could significantly mask the gels’ efficacy.  For example, if 80% of trial participants adhered to use of the gel, the microbicide would appear to have a 40% efficacy but its true efficacy would be 50%.  While avoiding these scenarios or similar dilution factors in future clinical trials is unlikely, the analysis shows that multiple sources of dilution acting simultaneously can significantly mask a microbicide’s true efficacy. Under conditions that have been observed in recent microbicide trials, gels with true efficacies of 50% or 75% would appear to have efficacies ranging from 16-33% or 28-50%, respectively. These results suggest that greater attention should be devoted to reducing and assessing the impact of efficacy dilution and to carefully selecting the effect size in the design of future microbicide trials.

Efficacy dilution in randomized placebo-controlled vaginal microbicide trials.  Mâsse BR, Boily MC, Dimitrov D, Desai K.  Emerg Themes Epidemiol. 2009 Oct 9;6:5.